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血浆中醋氯芬酸的高效液相色谱测定法及其在犬体内的药代动力学

[High performance liquid chromatographic assay for aceclofenac in plasma and its pharmacokinetics in dogs].

作者信息

Liu X Q, Chen X J, Zhao L H, Peng J H

机构信息

Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009.

出版信息

Yao Xue Xue Bao. 1997 Jul;32(7):546-8.

Abstract

A sensitive and simplified high performance liquid chromatographic procedure has been developed for the quantification of aceclofenac and its major metabolite in dog plasma. The recovery of aceclofenac was 91.3%-96.9%. The relative standard deviation was 3.69%-8.13%. The calibration curve was linear in the range from 0.050 microgram.ml-1 to 51.2 micrograms.ml-1 with gamma = 0.9998. The detection limit of the method is 10 ng.ml-1 for aceclofenac. Plasma concentrations of both aceclofenac and its major metabolite were simultaneously determined. After oral medication of aceclofenac to dogs at the dose of 2.5 mg.kg-1, the drug was absorbed rapidly and reached its peak level in plasma at about 12 min. The plasma drug concentration-time course conformed to a 2-compartment open model with a first order absorption. The mean value of T1/2 alpha and T1/2 beta for aceclofenac were 2.5 min and 137 min respectively. Plasma diclofenac concentration, a major metabolite of aceclofenac, reached its maximum at about 110 min, the mean Cmax for diclofenac was 3.2 micrograms.ml-1. The mean terminal elimination half-life for diclofenac was 140 min.

摘要

已开发出一种灵敏且简化的高效液相色谱法,用于定量犬血浆中醋氯芬酸及其主要代谢物。醋氯芬酸的回收率为91.3%-96.9%。相对标准偏差为3.69%-8.13%。校准曲线在0.050微克·毫升-1至51.2微克·毫升-1范围内呈线性,γ = 0.9998。该方法对醋氯芬酸的检测限为10纳克·毫升-1。同时测定了醋氯芬酸及其主要代谢物的血浆浓度。以2.5毫克·千克-1的剂量给犬口服醋氯芬酸后,药物吸收迅速,约12分钟时达到血浆峰值水平。血浆药物浓度-时间过程符合具有一级吸收的二室开放模型。醋氯芬酸的T1/2α和T1/2β平均值分别为2.5分钟和137分钟。醋氯芬酸的主要代谢物双氯芬酸的血浆浓度在约110分钟时达到最大值,双氯芬酸的平均Cmax为3.2微克·毫升-1。双氯芬酸的平均终末消除半衰期为140分钟。

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